Laboratory Studies
The fundamental step in diagnosing acute intermittent porphyria (AIP) is to demonstrate increased urinary porphobilinogen secretion. If a patient has no increased secretion of porphobilinogen, (ie, a level of 0-4 mg/L during acute symptoms), acute porphyria is eliminated as a cause of the neurovisceral symptoms. [15, 16]
A spot urine test for porphobilinogen can rapidly provide the diagnosis; these tests detect porphobilinogen at levels greater than 6 mg/L. A common error is to order a urine porphyrin screen. Porphobilinogen, a porphyrin precursor, usually is not included in a urine porphyrin screen; it must be ordered specially.
AIP patients have elevated porphobilinogen between attacks. However, in some patients with a remote (years ago) history of attacks, porphobilinogen can return to the reference range.
Elevation of urine porphyrins, especially coporphobilinogen, is observed. This is caused by spontaneous polymerization of porphobilinogen in the urine. Nonspecific (1-2 times reference range) elevation of urine porphyrins, especially coproporphyrins, is common and is not specific for porphyria. Stool porphyrins are within the reference range or mildly elevated.
Other nonspecific signs in an attack of AIP include the following:
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Hyponatremia
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Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)
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Mild leukocytosis
Although a defective enzyme causes AIP, measuring the activity of porphobilinogen deaminase is of little value. Approximately 10% of AIP patients will have normal activity because a different form of the enzyme is expressed in the hematopoietic tissues. The vast majority of patients with the defective enzyme do not have any symptoms of the disease.
Imaging Studies
Imaging studies are usually not helpful. Abdominal films will sometimes demonstrate an ileus. Findings on cranial computed tomography (CT) scan are normal.
Brain magnetic resonance imaging (MRI) scans occasionally show signs of increased edema in patients having very severe attacks. In patients with seizures, MRI may demonstrate parieto-occipital gyriform lesions on T2-weighted images that are characteristic of posterior reversible encephalopathy syndrome (PRES). [17]
Other Tests
Attacks of AIP are clinically indistinguishable from those of hereditary coproporphyria and variegate porphyria, and there are few evidence-based diagnostic strategies for these conditions. Whatley et al conducted a retrospective analysis of 467 unrelated patients to determine the diagnostic sensitivity of mutation analysis of the HMBS, CPOX, or PPOX gene. [18] Findings included the following [18] :
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In the presence of increased porphobilinogen excretion, plasma fluorescence scanning and the coproporphyrin ratio can identify the type of acute porphyria, with rare exceptions.
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In cases in which the porphobilinogen, 5-aminolevulinate, and porphyrin analyses are within reference intervals and in which there is high suspicion of a previous illness caused by an acute porphyria, mutation analysis of the HMBS gene followed by porphobilinogen deaminase assay is an effective strategy for diagnosis or exclusion of AIP.
Tables
Alcuronium *Alphaxalone Alphadolone Alprazolam Aluminium Preparations Amidopyrine Aminoglutethimide Aminophylline Amiodarone *Amitriptyline [Amphetamines] *Amylobarbitone Antipyrine *Auranofin *Aurothiomalate Azapropazone Baclofen *Barbiturates *Bemegride Bendrofluazide Benoxaprofen Benzbromarone [Benzylthiouracil] [Bepridil] Bromocriptine Busulphan *Butylscopolamine Captopril *Carbamazepine *Carbromal *Carisoprodol [Cefuroxime] [Cephalexin] [Cephalosporins] [Cephradine] [Chlorambucil] *Chloramphenicol *Chlordiazepoxide *Chlormezanone Chloroform *Chlorpropamide Cinnarizine Clemastine [Clobazam] [Clomipramine HCl] [Clonazepam] Clonidine HCl *Clorazepate Cocaine [Colistin] Co-trimoxazole |
Cyclophosphamide Cycloserine Cyclosporin Danazol *Dapsone Dexfenfluramine Dextropropoxyphene Diazepam *Dichloralphenazone *Diclofenac Na Dienoestrol Diethylpropion Dihydralazine *Dihydroergotamine Diltiazem *Dimenhydrinate *Diphenhydramine [Dothiepin HCl] Doxycycline *Dydrogesterone *Econazole NO3 *Enalapril Enflurane *Ergot compounds Ergometrine maleate Ergotamine tartrate *Erythromycin *Estramustine Ethamsylate *Ethanol Ethionamide *Ethosuximide *Ethotoin Etidocaine Etomidate Fenfluramine *Flucloxacillin *Flufenamic acid Flunitrazepam Flupenthixol Flurazepam *Frusemide *Glibenclamide *Glutethimide *Glipizide Gramicidin *Griseofulvin [Haloperidol] *Halothane *Hydantoins *Hydralazine *Hydrochlorothiazide *Hydroxyzine Hyoscine *Imipramine Iproniazid Isometheptene mucate [Isoniazid] Kebuzone Ketoconazole *Levonorgestrel Lignocaine *Lisinopril Loprazolam Loxapine *Lynestrenol Lysuride |
Maleate Maprotiline HCl Mebeverine HCl *Mecillinam *Medroxyprogesterone [Mefenamic acid] Megestrol acetate *Mephenytoin Mepivacaine *Meprobamate Mercaptopurine Mercury compounds Mestranol [Metapramine HCl] Methamphetamine Methohexitone [Methotrexate] [6] Methoxyflurane Methsuximide *Methyldopa *Methylsulphonal *Methyprylone Methysergide *Metoclopramide Metyrapone Mianserin HCl Miconazole [Mifepristone] Minoxidil *Nandrolone *Nalidixic acid Natamycin *Nandrolone [Nicergoline] *Nifedipine *Nikethamide Nitrazepam *Nitrofurantoin Nordazepam Norethynodrel *Norethisterone [Nortriptyline] Novobiocin *Oral contraceptives *Orphenadrine Oxanamide [Oxazepam] Oxybutynin HCl Oxycodone *Oxymetazoline *Oxyphenbutazone Oxytetracycline Paramethadione Pargyline *Pentazocine Perhexiline Phenacetin Phenelzine *Phenobarbitone Phenoxybenzamine *Phensuximide Phenylhydrazine *Phenytoin Pipebuzone Pipemidic Acid Piritramide *Piroxicam |
*Pivampicillin *Pivmecillinam Prazepam Prenylamine *Prilocaine *Primidone [Probenecid] *Progesterone Progabide Promethazine [Propanidid] *Pyrazinamide Pyrrocaine Quinalbarbitone Rifampicin Simvastatin Sodium aurothiomalate Sodium oxybate [Sodium valproate] *Spironolactone Stanozolol Succinimides *Sulfacetamide *Sulfadiazine *Sulfadimidine *Sulfadoxine *Sulfamethoxazole *Sulfasalazine *Sulfonylureas Sulfinpyrazone Sulpiride Sulthiame Sultopride *Tamoxifen *Terfenadine Tetrazepam *Theophylline *Thiopentone Na Thioridazine Tilidate Tinidazole *Tolazamide *Tolbutamide Tranylcypromine Trazodone HCl Trimethoprim [Trimipramine] Troxidone Valproate Valpromide Veralipride *Verapamil *Vibramycin Viloxazine HCl [Vinblastine] [Vincristine] Zuclopenthixol |
*These drugs have been associated with acute attacks of porphyria. †Bracketed [] drugs are those in which experimental evidence of porphyringenicity is conflicting. |
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Acetazolamide acetylcholine Actinomycin D [6] Acyclovir Adenosine monophosphate Adrenaline Alclofenac Allopurinol Alpha tocopheryl Acetate Amethocaine Amiloride Aminocaproic acid Aminoglycosides Amoxicillin Amphotericin Ampicillin Ascorbic acid Aspirin Atenolol Atropine Azathioprine Beclomethasone Benzhexol HCl Beta-carotene Biguanides [Bromazepam] Bromides Buflomedil HCl Bumetanide Bupivacaine Buprenorphine Buserelin Butacaine SO4 Canthaxanthin Carbimazole [Carpipramine HCl] Chloral hydrate [Chlormethiazole] [Chloroquine] [Chlorothiazide] Chlorpheniramine Chlorpromazine Ciprofloxacin Cisapride Cisplatin Clavulanic acid Clofibrate Clomiphene Cloxacillin Co-codamol Codeine phosphate Colchicine [Corticosteroids] Corticotrophin (adrenocorticotropic hormone [ACTH]) |
Coumarins Cyclizine Cyclopenthiazide Cyclopropane [Cyproterone acetate] Danthron Desferrioxamine Dexamethasone [Dextromoramide] Dextrose Diamorphine Diazoxide Dicyclomine HCl Diflunisal Digoxin Dihydrocodeine Dimercaprol Dimethicone Dinoprost Diphenoxylate HCl Dipyridamole [Disopyramide] Domperidone Doxorubicin HCl Droperidol [Estazolam] Ethacrynic acid Ethambutol [Ethinyl oestradiol] Ethoheptazine citrate Etoposide Famotidine Fenbufen [Fenofibrate] Fenoprofen Fentanyl Flucytosine Flumazenil Fluoxetine HCl Flurbiprofen Fluvoxamine Maleate Folic acid Fructose Fusidic acid Follicle-stimulating hormone Gentamicin Glafenine Glucagon Glucose Glyceryl trinitrate Goserelin Guanethidine Guanfacine HCl Haem arginate [Haloperidol] Heparin Heptaminol HCl Hexamine [Hydrocortisone] Ibuprofen Indomethacin Insulin Iron Josamycin [Ketamine] |
Ketoprofen Ketotifen Labetalol Luteinizing hormone–releasing hormone Liquorice Lithium Salts lofepramine Loperamide [Lorazepam] Magnesium-sulphate [Mebendazole] Mecamylamine Meclofenoxate HCl Meclozine Mefloquine HCl [Melphalan] Meptazinol Mequitazine Metformin Methadone [Methotrimeprazine] Methylphenidate Methyluracil Metipropranolol Metopimazine Metoprolol [Metronidazole] [Midazolam] Minaprine HCl Minaxolone Morphine Nadolol Naftidrofuryl Oxalate [Naproxen sodium] Natamycin Nefopam HCl Neostigmine Netilmicin Niflumic acid Nitrous oxide Norfloxacin Ofloxacin Oxolinic acid Oxybuprocaine [Oxyphenbutazone] Oxytocin [Pancuronium bromide] Paracetamol Paraldehyde Parapenzolate Br Penicillamine Penicillin Pentolinium Pericyazine Pethidine Phenformin Phenoperidine Phentolamine mesylate Pipotiazine |
Palmitate Piracetam Pirbuterol Pirenzepine Pizotifen [Prazosin] [Prednisolone] Primaquine Probucol Procainamide HCl Procaine Prochlorperazine Proguanil HCl Promazine Propantheline Br Propofol Propranolol Propylthiouracil [Proxymetacaine] Pseudoephedrine HCl Pyridoxine [Pyrimethamine] Quinidine Quinine [Ranitidine] Reserpine Resorcinol Salbutamol Senna Sodium bromide Sodium ethylenediaminetetraacetic acid Sodium fusidate Sorbitol Streptomycin Sulbutiamine Sulindac Sulfadoxine Suxamethonium Talampicillin Temazepam Tetracaine [Tetracyclines] Thiouracils Thyroxine Tiaprofenic acid Ticarcillin Tienilic acid Timolol maleate Tolazoline Tranexamic acid Triacetyloleandomycin Triamterene Triazolam [Trichlormethiazide] Trifluoperazine Trimeprazine Tartrate Trimetazidine HCl Tripelennamine Tubocurarine Vancomycin [Vincristine] Vitamins Warfarin sodium Zidovudine Zinc preparations |
*Bracketed [] drugs are those in which experimental evidence of porphyrin genicity is conflicting. |
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